Advanced glycation end products modulate transcriptional regulation in mesangial cells

Iehara, Noriyuki; Takeoka, Hiroya; Yamada, Yoshihiko; Kita, Toru; Doi, Toshio

doi:10.1038/ki.1996.424

Cited by 29 publications

(24 citation statements)

References 41 publications

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“…Thus, our study implicates that AGEs are a key factor in the synthesis of both HSP47 and collagens in diabetic nephropathy in vivo and in vitro. The mechanism of these processes remains unclarified, but we demonstrated that AGEs stimulate several novel transcription factors in gene expression for glomerulosclerosis (5). We have recently reported that Smad1 transcriptionally regulates of type IV collagen under AGE stimulation (14).…”

Section: Quantitation Of the Expression Ratio Of Hsp47/gapdh Mrna Andmentioning

confidence: 99%

“…AGEs, late compounds formed from early Amadori compounds produced during the Maillard reaction, slowly accumulate in various tissues. Direct evidence indicating the importance of AGEs in the progression of diabetic nephropathy has been reported previously (3)(4)(5). The administration of exogenous AGEs to normal rats induces glomerular hypertrophy and mesangial sclerosis, gene expression of matrix proteins, and production of various growth factors.…”

mentioning

confidence: 95%

“…AGE-BSA-AGE-BSA was prepared by the method described previously (5,21). BSA was incubated with glucose 6-phosphate for Ͼ60 days at 37°C.…”

Section: ј-Tggaccgcaacaacgcaatctatg-3ј)mentioning

confidence: 99%

“…Cell Culture-A glomerular mesangial cell line was established from glomeruli isolated from normal 4-week-old mice (C57BL/6JxSJL/J) and was identified according to a method described previously (4,5). The mesangial cells were plated on 100-mm plastic dishes (Nunc) that were maintained in B medium (a 3:1 mixture of minimal essential medium/ F12 modified with trace elements) supplemented with 1 mM glutamine, penicillin at 100 units/ml, streptomycin at 100 g/ml, and 20% fetal calf serum (Irvine Scientific).…”

Section: ј-Tggaccgcaacaacgcaatctatg-3ј)mentioning

confidence: 99%

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Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy

Ohashi

Abe

Takahashi

et al. 2004

Journal of Biological Chemistry

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Advanced glycation end products (AGEs) appear to contribute to the diabetic complications. This study reports the inhibitory effect of OPB-9195 (OPB), an inhibitor of AGEs formation, and the role of a collagen-specific molecular chaperone, a 47-kDa heat shock protein (HSP47) in diabetic nephropathy. Transgenic mice carrying nitric-oxide synthase cDNA fused with insulin promoter (iNOSTg) leads to diabetes mellitus. The iNOSTg mice at 6 months of age represented diffuse glomerulosclerosis, and the expression of HSP47 was markedly increased in the mesangial area in parallel with increased expression of types I and IV collagens. OPB treatment ameliorated glomerulosclerosis in the iNOSTg mice associated with the decreased expression of HSP47 and types I and IV collagens. The expression of transforming growth factor-␤ (TGF-␤) was increased in glomeruli of iNOSTg mice and decreased after treatment with OPB. To confirm these mechanisms, cultured mesangial cells were stimulated with AGEs. AGEs significantly increased the expression of HSP47, type IV collagen, and TGF-␤ mRNA. Neutralizing antibody for TGF-␤ inhibited the overexpression of both HSP47 and type IV collagen in vitro. In conclusion, AGEs increase the expression of HSP47 in association with collagens, both in vivo and in vitro. The processes may be mediated by TGF-␤.

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Section: Quantitation Of the Expression Ratio Of Hsp47/gapdh Mrna Andmentioning

confidence: 99%

mentioning

confidence: 95%

“…AGE-BSA-AGE-BSA was prepared by the method described previously (5,21). BSA was incubated with glucose 6-phosphate for Ͼ60 days at 37°C.…”

Section: ј-Tggaccgcaacaacgcaatctatg-3ј)mentioning

confidence: 99%

Section: ј-Tggaccgcaacaacgcaatctatg-3ј)mentioning

confidence: 99%

See 2 more Smart Citations

Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy

Ohashi

Abe

Takahashi

et al. 2004

Journal of Biological Chemistry

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“…The a-SMA promoter reporter plasmid (SMA-Luc) contains 1074 bp of the proximal 5 0 -flanking region plus 43 bp 5 0 -untranslated region of the a-SMA gene 19 that is subcloned into the luciferase reporter vector (Promega).…”

Section: Plasmid Constructsmentioning

confidence: 99%

Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy

Matsubara

Abe

Arai

et al. 2006

Laboratory Investigation

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Diabetic nephropathy is the leading cause of end-stage renal disease, and glomerular mesangial matrix expansion is the hallmark in diabetic nephropathy. However, the precise mechanism for the development of mesangial matrix expansion has remained unknown. The key component involved in mesangial matrix expansion is type IV collagen (Col4). Recently, we have reported that Smad1 transcriptionally regulates expression of Col4 under diabetic conditions in vitro. Here we show that this direct regulator of Col4 also plays a crucial role for mesangial matrix expansion in vivo. Streptozotocin-induced diabetic rats are the model of incipient diabetic nephropathy, and showed various levels of mesangial matrix expansion at 24 weeks. The glomerular expression of Smad1 was significantly increased in diabetic rats with more mesangial matrix expansion by Western blot and immunohistochemical analysis. Furthermore, the glomerular expression of Smad1 was closely correlated with the glomerular expression of Col4 and smooth muscle alpha actin (a-SMA), while albuminuria or glomerular filtration rate was not correlated with mesangial matrix expansion. We also found that urinary excretion of Smad1 was closely associated with the severity of mesangial matrix expansion. In cultured mesangial cells expression of Smad1 upregulated the transcriptional activity of key molecules in mesangial matrix expansion, such as Col4 and a-SMA. These data indicate the critical involvement of Smad1 in mesangial matrix expansion in the early phase of diabetic nephropathy. Our data imply that urinary Smad1 might be a representative diagnostic marker for mesangial matrix expansion in diabetic nephropathy.

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A novel transcription factor is correlated with both glomerular proliferation and sclerosis in the rat renal ablation model

et al. 1997

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Glomerular accumulation of the extracellular matrix (ECM) with subsequent sclerosis is a common finding in most progressive renal diseases. Recently MSW (Mouse South Western) protein was cloned by its ability to bind the bidirectional promoter of the collagen IV genes. This protein was also reported as the large subunit of the DNA replication complex A1, as well as the promoter binding protein of corticotropin‐releasing hormone and the angiotensinogen gene. To investigate the mechanism of accumulation of the ECM as it relates to glomerular cellular events, the expression of MSW protein was studied in the remnant kidney model. Progressive expression of MSW protein was found in the glomerular sclerotic lesion at week 4 and at later time points after renal ablation. The expression of proliferating cell nuclear antigen (PCNA) and type IV collagen was also correlated with the expression of MSW protein by immunofluorescence. RNA dot blot analysis also showed that the expression of MSW mRNA was increased at week 7 in association with the augmented expression of type IV collagen. These results, taken together, suggest that MSW protein plays an important role in the regulation of type IV collagen gene expression in vivo and may contribute to glomerular cell proliferation and the development of glomerulosclerosis.© 1997 by John Wiley & Sons, Ltd.

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Advanced glycation end products modulate transcriptional regulation in mesangial cells

Cited by 29 publications

References 41 publications

Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy

Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy

Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy

A novel transcription factor is correlated with both glomerular proliferation and sclerosis in the rat renal ablation model

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